The present invention relates to novel (3-amino-1-propynyl)methylthiothiophene compounds, pharmaceutical compositions containing the compounds and to the use of the compounds for the treatment of central cholinergic dysfunction.
Senile Dementia of the Alzheimer's type (SDAT) is a neurodegenerative disease which results in the progressive impairment of memory. Post mortem autopsies of brain tissue from SDAT patients have shown a marked decrease in cholinergic neurons. Taken together these observations form the basis for the cholinergic hypothesis of memory loss. A series of chemical synthesis projects have been initiated in the geriatric program to discover selective cholinergic agonists to ameliorate the symptoms of this degenerative disease.
In this respect, a number of derivatives of the cholinergic agent, oxotremorine, have been synthesized. Resul, B. and co workers, Eur. J. Med. Chem., 1982, 17, 317 report the synthesis of N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acet-amide, referred to as BM-5, which acts as an antagonist at some muscarinic sites while being an agonist at most others. It has been suggested that this type of compound may be useful for the therapy of Alzheimer-type dementia.